6-24209027-T-C

Position:

• chr6-24209027-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016356.5(DCDC2):​c.923-3925A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 152,162 control chromosomes in the GnomAD database, including 1,055 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.11 (1055 hom., cov: 32)
• Consequence: DCDC2 NM_016356.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.250

Genes affected

DCDC2 (HGNC:18141): (doublecortin domain containing 2) This gene encodes a doublecortin domain-containing family member. The doublecortin domain has been demonstrated to bind tubulin and enhance microtubule polymerization. This family member is thought to function in neuronal migration where it may affect the signaling of primary cilia. Mutations in this gene have been associated with reading disability (RD) type 2, also referred to as developmental dyslexia. Alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jan 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCDC2	NM_016356.5	c.923-3925A>G		intron_variant		ENST00000378454.8	NP_057440.2
DCDC2	NM_001195610.2	c.923-3925A>G		intron_variant			NP_001182539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCDC2	ENST00000378454.8	c.923-3925A>G		intron_variant		1	NM_016356.5	ENSP00000367715.3

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17161 AN: 152044 Hom.: 1054 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.0917

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.0453

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.0487

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.130

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.113 AC: 17181 AN: 152162 Hom.: 1055 Cov.: 32 AF XY: 0.109 AC XY: 8083 AN XY: 74400

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.0915

Gnomad4 ASJ AF: 0.147

Gnomad4 EAS AF: 0.0452

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.0487

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.130

Alfa AF: 0.0358 Hom.: 34

Bravo AF: 0.118

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.2
DANN	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9467076; hg19: chr6-24209255;